Maternal mosaicism involving different 18p (micro-)deletions transmitted as a typical 18p deletion to a patient with De Grouchy syndrome I

Complete loss of the short arm of chromosome 18 (18p- deletion syndrome or DeGrouchy syndrome I) causes cognitive impairment, ptosis, structural brain malformations, and other features. We describe a family in which the mother of a child with 18p- syndrome showed several different mosaic 18p deletions. Index patient was a 10-year-old girl with intellectual disability (IQ 60), ptosis, white matter abnormalities and mild facial dysmorphism. Her mother and two older brothers were healthy but had mild learning disability.
SNP array in the girl showed near-total loss of 18p (14,7 MB deletion). Chromosome analysis of the mother indicated a normal karyotype in 20/30 metaphases, with 18p deletion in 10/30 metaphases (33%). Interphase FISH with probes for the subtelomeric (D18S552, Vysis) and a more proximal region (RP11-620N7, Empire Genomics, maps to 18p11.23) revealed a more complex mosaic with two distinct cell lines: ~70% of cells carried a microdeletion of the 18p subtelomeric region, and ~30% the large 18p- deletion (involving 18p11.23). In oral buccosa of the mother the ratio was 95% microdeletion and 5% larger deletion. The karyotypes including FISH of the father and one brother were normal. SNP array analysis in the mother and FISH analysis in the second brother are currently underway. While deletions involving chromosome 18 are common, mosaicism for structural rearrangements is exceedingly rare. This is the first report of mosaicism for two different size deletions of chromosome 18p with vertical transmission of the larger deletion to a symptomatic daughter.